There are few neuropsychological or neuroimaging studies of HIV-positive children with "slow progression". "Slow progressors" are typically defined as children or adolescents who were vertically infected with HIV, but who received no or minimal antiretroviral therapy. We compared 12 asymptomatic HIV-positive children (8 to 12 years) with matched controls on a neuropsychological battery as well as diffusion tensor imaging in a masked region of interest analysis focusing on the corpus callosum, internal capsule and superior longitudinal fasciculus. The "slow progressor" group performed significantly worse than controls on the Wechsler Abbreviated Scale of Intelligence Verbal and Performance IQ scales, and on standardised tests of visuospatial processing, visual memory and executive functioning. "Slow progressors" had lower fractional anisotropy (FA), higher mean diffusivity (MD) and radial diffusivity (RD) in the corpus callosum (p= <0.05), and increased MD in the superior longitudinal fasciculus, compared to controls. A correlation was found between poor performance on a test of executive function and a test of attention with corpus callosum FA, and a test of executive function with lowered FA in the superior longitudinal fasiculus. These data suggest that demyelination as reflected by the increase in RD may be a prominent disease process in paediatric HIV infection.

Background: Prevalence and characteristics of fetal alcohol syndrome (FAS) and total fetal alcohol spectrum disorders (FASD) were studied in a second sample of three South African rural communities to assess change. Methods: Active case ascertainment focused on children with height, weight and/or head circumference ≤25th centile and randomly-selected children. Final diagnoses were based on dysmorphology, neurobehavioral scores, and maternal risk interviews. Results: Cardinal facial features, head circumference, and total dysmorphology scores differentiated specific FASD diagnostic categories in a somewhat linear fashion but all FASD traits were significantly worse than those of randomly-selected controls. Neurodevelopmental delays were significantly worse for children with FASD than controls. Binge alcohol use was clearly documented as the proximal maternal risk factor for FASD, and significant distal risk factors were: low body mass, education, and income; high gravidity, parity, and age at birth of the index child. FAS rates continue to extremely high in these communities at 89–129 per 1000 children. Total FASD affect 196–276 per 1000 or 20–28% of the children in these communities. Conclusions: Very high rates of FASD persist in these general populations where regular, heavy drinking, often in a binge fashion, co-occurs with low socioeconomic conditions.

Background The prevalence and characteristics of the continuum of diagnoses within fetal alcohol spectrum disorders (FASD) were researched in a fifth sample in a South African community. Methods An active case ascertainment approach was employed among all first grade learners in this community (n=862). Following individual examination by clinical geneticists/ dysmorphologists, cognitive/behavioral testing, and maternal interviews, final diagnoses were made in multidisciplinary case conferences. Results Physical measurements, cardinal facial features of FAS, and total dysmorphology scores clearly differentiated diagnostic categories in a consistent, linear fashion, from severe to mild. Neurodevelopmental delays and behavioral problems were significantly worse for each of the FASD diagnostic categories, although not as consistently linear across diagnostic groups. Alcohol use was documented by direct report from the mother in 71% to 100% of cases in specific diagnostic groups. Significant distal maternal risk factors in this population are: advanced maternal age at pregnancy; low height, weight, and body mass index (BMI); small head circumference; low education; low income; and rural residence. Even when controlling for socioeconomic status, prenatal drinking correlates significantly with total dysmorphology score, head circumference, and five cognitive and behavioral measures. In this community, FAS occurs in 59 – 79 per 1,000 children, and total FASD in 170 – 233 per 1,000 children, or 17% to 23%. Conclusions Very high rates of FASD continue in this community where entrenched practices of regular binge drinking co-exist with challenging conditions for childbearing and child development in a significant portion of the population.

Purpose The variant spectrum and the phenotype of X-linked Kabuki syndrome type 2 (KS2) are poorly understood. Methods Genetic and clinical details of new and published individuals with pathogenic KDM6A variants were compiled and analyzed. Results Sixty-one distinct pathogenic KDM6A variants (50 truncating, 11 missense) from 80 patients (34 males, 46 females) were identified. Missense variants clustered in the TRP 2, 3, 7 and Jmj-C domains. Truncating variants were significantly more likely to be de novo. Thirteen individuals had maternally inherited variants and one had a paternally inherited variant. Neonatal feeding difficulties, hypoglycemia, postnatal growth retardation, poor weight gain, motor delay, intellectual disability (ID), microcephaly, congenital heart anomalies, palate defects, renal malformations, strabismus, hearing loss, recurrent infections, hyperinsulinism, seizures, joint hypermobility, and gastroesophageal reflux were frequent clinical findings. Facial features of over a third of patients were not typical for KS. Males were significantly more likely to be born prematurely, have shorter stature, and severe developmental delay/ID. Conclusion We expand the KDM6A variant spectrum and delineate the KS2 phenotype. We demonstrate that the variability of the KS2 phenotypic depends on sex and the variant type. We also highlight the overlaps and differences between the phenotypes of KS2 and KS1.